炎症因子在糖尿病溃疡中的作用及中医药治疗前景

Role of inflammatory factors in diabetic ulcers and prospects of traditional Chinese medicine intervention

背景:糖尿病溃疡是糖尿病常见并发症,表现为足部溃疡合并感染,治疗周期长,致残率和病死率较高,给患者和社会医疗带来了沉重的负担。目的:综述中医药治疗糖尿病溃疡创面的作用机制和最新治疗进展,为其进一步理论研究和临床合理应用提供依据。方法:检索中国知网、万方和PubMed数据库收录的相关文献。中文检索词为“糖尿病溃疡,中药,炎症,白细胞介素1β,白细胞介素6,肿瘤坏死因子,超敏C反应蛋白,干扰素γ,白细胞介素4,白细胞介素10”。英文检索词为“Diabetes Ulcer,Medicinal herb,Inflammation,interleukin-1β,interleukin-6,tumor necrosis factor,hypersensitive C-reactiveprotein,γ-interferon,Interleukin-4,interleukin-10”,最终纳入75篇文献进行归纳总结。结果与结论:(1)机体的高糖环境会提高促炎细胞因子水平,使糖尿病溃疡创面长期处于慢性炎症反应状态,难以愈合甚至不愈合。(2)中医在与糖尿病溃疡的长期斗争中总结出许多经验,目前不仅将糖尿病溃疡分湿热毒盛证、血脉瘀阻证、热毒伤阴证和气血两虚证4个证型以及治疗的代表方剂,还根据糖尿病溃疡的临床特点将糖尿病溃疡分为初、中、后3期并提出“清法”“温清并用”和“养法”三期不同治法。在中医辨证分型和分期的指导下,中药单体、提取物及中药复方通过下调促炎因子的表达和(或)上调抗炎因子的表达抑制炎症反应,促进糖尿病溃疡的愈合。与现代医学相比,中药物优价廉、疗效好、不良反应小,在治疗糖尿病溃疡方面有着显著的优势。(3)治疗糖尿病溃疡的中药单体、提取物及中药复方众多,如白芷、姜黄素、改良冲和膏、三黄血竭方和疮疡Ⅰ号方等,归纳后发现治疗糖尿病溃疡的中药以清热解毒、活血化瘀和敛疮生肌药为主,且中药复方的使用频率、治疗范围和治疗效果明显优于中药单体和提取物,其中最常用的是治疗湿热毒盛证的三黄血竭方和疮疡Ⅰ号方以及治疗非缺血型糖尿病溃疡的紫朱软膏。(4)然而中医药治疗糖尿病溃疡也存在一定的不足,首先,目前关于糖尿病溃疡的临床证候学研究较少;其次,中医药治疗糖尿病溃疡的中药单体、提取物和复方种类繁多,研究不够深入;最后,中医药治疗糖尿病溃疡的机制研究仍处于初步探索阶段,作用机制仍需进一步探索。(5)未来应加强中药药理学和糖尿病溃疡的临床证候学研究,分析中医药治疗糖尿病溃疡的潜在靶点和相关信号通路,充分发挥中医药多靶点、多通路、多层次及多系统的治疗优势,研制出疗效显著、有效成分和作用靶点明确的中药。

BACKGROUND:Diabetic ulcers are a common complication of diabetes mellitus,which is manifested as foot ulcers complicated with infection,long treatment cycle,high disability rate and mortality rate,and brings a heavy burden to patients and social care.OBJECTIVE:To review the mechanism of action and the latest treatment progress of traditional Chinese medicine(TCM)in the treatment of diabetic ulcers,and to provide a basis for further theoretical research and clinical application.METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature using the keywords of“diabetic ulcer,medicinal herb,inflammation,interleukin-1β,interleukin-6,tumor necrosis factor,hypersensitive C-reactive protein,γ-interferon,interleukin-4,interleukin-10”in Chinese and English,respectively.The relevant literature in recent years was searched,and finally 75 articles were included for review.RESULTS AND CONCLUSION:The high glucose environment of the body will increase the level of pro-inflammatory cytokines,so that diabetic ulcer wounds are in a state of chronic inflammatory response for a long time,and difficult to heal or even not heal.TCM has summed up a lot of experience in the long-term struggle with diabetic ulcer.At present,TCM divides diabetic ulcers into four syndrome types:dampness and heat poison syndrome,blood and blood stasis obstruction pattern,heat poison injury Yin pattern,and Qi and blood deficiency syndrome,as well as representative prescriptions for treatment.According to their clinical characteristics,diabetic ulcers can be also divided into three stages:primary,middle and late stages.Different treatment methods are proposed:“clear method,”“warm and clear combined use”and“maintenance method.”Under the guidance of dialectical typing and staging of TCM,TCM monomers,extracts and compounds inhibit the inflammatory response and promote the healing of diabetic ulcers by down-regulating the expression of pro-inflammatory factors and/or up-regulating the expression of anti-inflammatory factors.Compared with modern medicine,TCM has significant advantages in the treatment of diabetic ulcers.There are many TCM monomers,extracts and compounds for the treatment of diabetic ulcers,such as angelica,curcumin,improved Chonghe ointment,Sanhuang blood exhaustion prescription and sore-ulcer I.formula,etc.It has been found that TCM for the treatment of diabetic ulcers is mainly heat-clearing and detoxifying,invigorating blood circulation and removing blood stasis,and amassing sores and muscle-building drugs,and the frequency of use,treatment scope and therapeutic effect of TCM compounds are obviously better than those of TCM monomers and extracts.Among them,the most commonly used are the Sanhuang blood exhaustion prescription and the sore-ulcer I as well as prescription for the treatment of damp heat toxicity syndrome and Zizhu ointment for the treatment of non-ischemic diabetic ulcers.However,there are also some shortcomings in the treatment of diabetic ulcers with TCM.First,there are few clinical syndrome studies on diabetic ulcers.Secondly,there are a wide variety of TCM monomers,extracts and compounds for the treatment of diabetic ulcers,and the relevant research is insufficiently in-depth.Finally,the research on the mechanism underlying TCM treatment of diabetic ulcers is still in the preliminary exploration stage,and the mechanism of action still needs to be further explored.In the future,it is necessary to strengthen the research on the pharmacology of TCM and the clinical syndrome of diabetic ulcers,analyze the potential targets and related signaling pathways of TCM in the treatment of diabetic ulcers,give full play to the therapeutic advantages of TCM with multiple targets,multiple pathways,multiple levels and multiple systems,and develop TCM with significant efficacy,active ingredients and clear targets.